Ovarian cancer remains one of the leading causes of cancer-related mortality among women because of its asymptomatic early course, delayed diagnosis, and frequent presentation at advanced stages. Germline and somatic mutations in the BRCA1 and BRCA2 genes significantly increase the risk of ovarian cancer by impairing homologous recombination DNA repair, resulting in genomic instability. Beyond their role in carcinogenesis, BRCA mutations have become important prognostic and predictive biomarkers, influencing treatment response and clinical outcomes. This review summarizes current evidence regarding the impact of BRCA1/2 status on prognosis and therapeutic strategies in ovarian cancer.
A literature review was conducted using the PubMed and Scopus databases. English-language articles published between 2016 and 2026 were identified using combinations of the keywords
ovarian cancer
,
BRCA1
,
BRCA2
,
PARP inhibitors
,
homologous recombination deficiency
, and
treatment
. Original studies, systematic reviews, meta-analyses, and relevant clinical trials were included.
The available evidence demonstrates that patients carrying BRCA1 or BRCA2 mutations generally experience improved progression-free survival and, in many studies, prolonged overall survival compared with non-carriers. This survival advantage is largely attributed to increased sensitivity to platinum-based chemotherapy and the efficacy of PARP inhibitors, which exploit synthetic lethality in homologous recombination-deficient tumors. The literature also emphasizes the importance of universal BRCA testing to optimize treatment selection, identify candidates for maintenance PARP inhibitor therapy, and facilitate genetic counseling. In addition, emerging mechanisms of resistance to PARP inhibitors remain a significant therapeutic challenge.
BRCA1/2 mutation status is a key biomarker in the management of ovarian cancer, supporting personalized treatment strategies and improving patient outcomes. Further research is needed to identify novel predictive biomarkers, overcome therapeutic resistance, and develop more effective targeted therapies.
Weronika Pawul, Paulina Opoka, Agata Dusza et al.· Frontiers in Oncology· 0 citations
Breast cancer (BC) remains the most common malignant tumor in women worldwide and a leading cause of cancer-related deaths. Despite therapeutic advances, patients with advanced BC, particularly triple-negative breast cancer (TNBC), still face limited effective treatment options. Antibody-drug conjugates (ADCs) represent a compelling strategy that combines precise tumor targeting with cytotoxic payloads, effectively bridging targeted delivery with microenvironmental disruption. Datopotamab deruxtecan (Dato-DXd), a Trop-2-targeted ADC, has demonstrated encouraging clinical activity. Preclinical evidence suggests that Dato-DXd may modulate the tumor microenvironment (TME) through potential induction of immunogenic cell death (ICD), providing a biological rationale for investigating synergistic combinations with immunotherapy.
A systematic review was conducted in accordance with PRISMA guidelines using the PubMed, Web of Science, and ClinicalTrials databases. The inclusion criteria targeted relevant clinical studies published between 2024 and 2026. Ultimately, after a thorough analysis, one randomized controlled trial (RCT) and one single-arm study met the eligibility criteria and were included in the review.
Data analysis from the Phase III TROPION-Breast01 trial demonstrated that Dato-DXd significantly improved objective response rate (ORR) and median progression-free survival (PFS) compared to investigator’s choice chemotherapy in patients with HR+/HER2- breast cancer. In the Phase I TROPION-PanTumor01 trial, Dato-DXd showed promising clinical activity in both HR+/HER2- breast cancer and TNBC cohorts. Regarding safety, Dato-DXd was associated with a lower incidence of grade ≥ 3 adverse events compared to standard chemotherapy in the randomized setting, although low-grade toxicities such as stomatitis and nausea remained common.
Dato-DXd demonstrates robust clinical activity in patients with BC, providing superior disease control with a favorable safety profile compared to conventional chemotherapy. Beyond direct tumor cell ablation, its mechanism of action includes a potent bystander killing effect, while preclinical data suggest that the induction of ICD may contribute to reshaping a heterogeneous TME. Future research is needed to correlate these preclinical mechanistic hypotheses with clinical outcomes. The limited number of available RCTs and Real-World Evidence (RWE) studies underscores the need to raise awareness and conduct further research to identify predictive biomarkers and evaluate combinations with immune checkpoint inhibitors to optimize personalized treatment regimens.
https://www.crd.york.ac.uk/prospero/
, identifier CRD420261408796.
Julia Piekarz, Natalia Picheta, Jakub Pobideł et al.· Frontiers in Immunology· 0 citations
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